GW 9578

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor found predominantly in the liver that is involved in the regulation of lipid homeostasis.^1,2 Activation of PPARα results in expression of a variety of genes, particularly those involved in fatty acid β-oxidation, binding, and transport. ³ GW 9578 is a potent agonist of PPARα that activates the murine and human receptors with EC₅₀ values of 0.005 and 0.05 µM, respectively.⁴ GW 9578 is highly selective for PPARα compared to PPARγ and PPARδ, which it activates in murine at EC₅₀ values of 0.15 and 2.6 µM, respectively and in human at 1.0 and 1.4 µM, respectively.⁴ GW 9578 is a potent lipid lowering agent that may reduce insulin resistance. When 0.2 mg/kg GW 9578 was given orally once daily for three days, serum total LDL cholesterol was decreased 40-60% in male Sprague-Dawely rats.⁴ Obese Zucker rats treated with 5 mg/kg GW 9578 for nine days had markedly reduced serum insulin concentrations compared to controls.⁵

WARNING This product is not for human or veterinary use.

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2. Lemberger, T., Desvergne, B., and Wahli, W. Peroxisome proliferator-activated receptors: A nuclear receptor signaling pathway in lipid physiology. Annu. Rev. Cell Dev. Biol. 12, 335-363 (1996).

3. Mandard, S., Müller, M., and Kersten, S. Peroxisome proliferator-activated receptor α target genes. Cell. Mol. Life Sci. 61(4), 393-416 (2004).

4. Brown, P.J., Winegar, D.A., Plunket, K.D., et al. A ureido-thioisobutyric acid (GW9578) is a subtype-selective PPARα agonist with potent lipid-lowering activity. J. Med. Chem. 42(19), 3785-3788 (1999).

5. Guerre-Millo, M., Gervois, P., Raspé, E., et al. Peroxisome proliferator-activated receptor α activators improve insulin sensitivity and reduce adiposity. The Journal of Biological Chemisty 275(22), 16638-16642 (2000).